tbuckley/cabot-search huggingface dataset:
Sequential metastasis-directed therapy (MDT) for oligometastatic prostate cancer (Oligo PCa) assessed by PET-based imaging.
Authors: Alberto Carretero-González, Daniel Kwon, Nonna Shakhnazaryan, Julian C. Hong, Osama Mohamad, Mary Uan-Sian Feng, Ivan de Kouchkovsky, Hala Borno, Rohit Bose, Jonathan Chou, Arpita Desai, Lawrence Fong, Terence W. Friedlander, Vadim S Koshkin, Felix Y Feng, Rahul Raj Aggarwal, Thomas A. Hope, Eric Jay Small
Journal: Journal of Clinical Oncology (2023)

5032 Background: Prostate specific membrane antigen (PSMA) and F-18-Fluciclovine PET imaging have high sensitivity for the detection of prostate cancer (PCa) metastases. MDT with stereotactic body radiation therapy (SBRT) to PET-detected Oligo PCa has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT). However, in those patients (pts) who ultimately develop oligoprogressive disease following MDT, the utility of subsequent courses of MDT has not been well defined. Methods: A single institution retrospective review was undertaken to describe outcomes following ≥2 courses of PET-guided SBRT in pts with Oligo PCa. Pts included in this analysis had undergone initial SBRT for ≤5 PCa lesions detected on PSMA or Fluciclovine PET, and subsequently underwent ≥1 additional course of SBRT at progression. Baseline data collected included stage, PSA level, Gleason Score, tracer type, and concurrent systemic therapy. Endpoints collected for each SBRT course included PSA decline ≥50% (PSA50), PFS, and systemic therapy change free survival (RxFS) (initiation of ADT, or for pts already on ADT, addition of an androgen signaling inhibitor). Association of factors with PFS after SBRT2 were analyzed using multivariable Cox proportional-hazards models. Results: 34 pts underwent ≥2 courses of MDT (SBRT1, SBRT2). At SBRT2, progression was identified by PSMA-PET in 26 (77%) pts, and by Fluciclovine-PET in 8 (23%). With SBRT2, 18 (53%) had a concurrent systemic therapy change; 10 (29%) did not receive any systemic therapy. 12 pts subsequently underwent SBRT3. Progression was detected by PSMA PET in 9 (75%) and Fluciclovine PET in 3 (25%). Clinical outcomes are summarized in the table. In the multivariable analysis, predictors associated with PFS following SBRT2 were 1) PSA decline at SBRT1 (HR 1.10, 95% CI 1.05-1.16, P&lt;0.001) and 2) PSA doubling time (PSADT) &lt; 12 months at the time of SBRT2 (HR 11.52, 95% CI 1.36-97.38, P 0.025). Overall, from SBRT1 to last follow-up (median 25.2 months), 23 (68%) pts remained ADT-free (14 after SBRT2; 9 after SBRT3). Conclusions: Serial MDT for Oligo PCa detected on PSMA or Fluciclovine PET is feasible and results in PSA declines, independent of change in systemic therapy. There is a persistent but diminishing benefit of MDT over successive courses. Overall, 2/3 of pts were able to postpone the use of ADT. PSA decline at SBRT1 and PSADT at SBRT2 may be biomarkers for SBRT2 benefit. Despite the retrospective nature of this study and cohort heterogeneity, these data provide a rationale for serial SBRT in Oligo PCA, and the need for larger, prospective studies of this strategy. [Table: see text]
Mutation-site localized non-B DNA burden and survival heterogeneity in early-stage pancreatic cancer.
Authors: Qi Xu, Jeanne Kowalski-Muegge
Journal: Journal of Clinical Oncology (2023)

4166 Background: Pancreatic cancer is a highly aggressive disease with a poor prognosis, and one in which most measure of genomic instability (e.g., tumor mutation burden (TMB), fraction of genome altered (FGA)) have thus far, not proven informative in differentiating survival. Non-B DNA are alternative DNA forms that deviate from the canonical B-DNA structure with potential to increase susceptibility to mutations, leading to the development of cancer. The role of non-B in pancreatic cancer has not been fully explored. Herein, we investigate the relationship between gene mutation sites co-localized with non-B DNA motifs in terms of survival and B-DNA features. Methods: Using TCGA data, we derived a genome-wide mutation signature on 104 early-stage pancreatic patients. We introduced a metric, mutation-localized non-B burden (MLNB) by the number of non-b motifs containing mutation sites, normalized to the number of mutations and motif library size. We applied MLNB to patient-specific mutation signatures to derive an MLNB burden for non-B DNA structure motifs: G-quadruplexes (G4), Z-DNA, inverted repeats (IR), mirror repeats (MR), direct repeats (DR), and short tandem repeats (STR). We performed a cluster analysis on MLNB and compared groups based on overall survival (OS) in months (mos) using a log-rank test. Comparisons of B-DNA-derived molecular features among clusters were performed using a Kruskal-Wallis and Fisher Exact test. Results: Among the 104 early-stage pancreatic patients with a mutation signature, MLNB clustering resulted in six patient clusters that differentiated by non-B DNA structure, with DR burden the longest OS cluster (n=23, median OS=30mos), significantly (p &lt; 0.05) differing as compared to IR (n=23, median OS=15 mos), STR (n=20, median OS=16mos), MR with lack of IR (n=14, median OS=13mos) and MR with IR (n=16, median OS=8mos). A mix of Z-DNA and G4 burden defined a cluster with shorter OS (n=22, median OS=14mos) as compared to DR, though not significant. Patients with the longest OS, MLNB-DR burden cluster had mutation signatures enriched in MAPK and Notch signaling pathways, as compared to the other clusters enriched with double-stranded break and mismatch repair (IR), hedgehog and WNT signaling (STR), and interleukin-4 signaling (MR) pathways. Among all clusters, CDKN2A deletion was most prevalent except for MLNB-DR burden cluster. No Significant differences were found between the MLNB clusters with age, race gender, KRAS and TP53 mutations, FGA, TMB, tumor purity, Bailey and Moffit subtypes. Conclusions: Our results point towards the potential use of MLNB as an emerging marker of site-structure genomic instability. Considering that triplex DNA is emerging as a marker genomic instability, and that we distinguish between two MR groups based on IR burden, our results may provide insights into various instability mechanisms associated with poor survival in pancreatic cancer.
Evaluating social vulnerability impact on care and prognosis of head &amp; neck-nervous system cancers in the US.
Authors: Salim Lutfallah, David Fei-Zhang, Daniel Chelius, Jill D'Souza, Jonas Paludo, Michael W. Ruff, Jeffrey Rastatter, Anthony Sheyn
Journal: Journal of Clinical Oncology (2023)

6526 Background: In the current literature, the association between social determinants of health (SDH) and head &amp; neck-nervous system cancer (HNNsC) is limited by the narrow scope of SDH assessed and the broad classifications of HNNsC. Our study utilizes the CDC-Social Vulnerability Index (SVI) to assess both the individual and collective impact of four social determinant themes on various HNNsC in US adults. Methods: This study utilized the SEER database to evaluate 116,373 adult patients from 1975-2017 who presented with HNNsC. Patients were assigned SVI scores based on county-of-residence at the time of diagnosis, encompassing total-SVI score and 4 sub-scores of socioeconomic status, minority-language status, household composition, and housing-transportation. Using these scores, univariate linear regressions were used to assess patient care (months of follow-up) and prognosis (months of survival). Results: As total-SVI score increased, decreases in months of follow-up (MOF) and months of survival (MOS) were observed for many HNNsC tumors (p less than 0.001) when comparing the lowest to highest vulnerability cohorts. There was a decrease ranging from 3.55-36.6% in the MOF, with the largest decreases occurring in embryonal, anaplastic oligodendroglioma, and anaplastic ependymoma tumor types, with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Similarly, there was a decrease ranging from 6.90-45.81% in the MOS, with the largest decreases occurring in anaplastic ependymoma, anaplastic astrocytoma, and pilocytic astrocytoma tumor types with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Increases in vulnerability within SDH themes contributed significantly to these total-SVI trends in MOF and MOS, with each social determinant impacting different disease classes to varying extents. Socioeconomic status was the most impactful sub-score for MOF in nine of fourteen disease classes, followed by housing-transportation and household composition, each leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Similarly, socioeconomic status was the most impactful sub-score for MOS in eight of fourteen disease classes, followed by housing-transportation leading the impact of three of fourteen disease classes, household composition leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Conclusions: The results of this study show that with increasing social vulnerability, there is a significant decrease in both the care (follow-up) and the prognosis (survival) of US adults with HNNsC and highlight which SDH contributes more to disparities.
Clinical remission rates in patients with epithelial ovarian cancer in the pandemic versus the pre-pandemic period.
Authors: Natalie Shammas, Amrita Mukherjee, Lanfang Xu, Kimberly L. Cannavale, Elizabeth A. Szamreta, Matthew Monberg, Melissa Hodeib, Chun Chao
Journal: Journal of Clinical Oncology (2023)

e17541 Background: The COVID-19 pandemic presented challenges for patients with ovarian cancer (OC). The objectives of this study were to compare patient remission outcomes following first-line treatment before and after the onset of the pandemic, and to evaluate potential racial/ethnic disparities in remission outcomes during the pandemic. Methods: This retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC), a large, integrated healthcare delivery system. Patients diagnosed with Stage I-IV epithelial ovarian cancer 01/01/2017-06/30/2021 were included. Pre and post pandemic periods were designated using 03/04/2020 as the cut-off. Data on cancer characteristics and treatment were obtained from KPSC’s electronic medical records. Chart review was conducted to collect data on complete and clinical remission (complete + partial remission) after first course of treatment. Imaging showing no evidence of disease and normal CA 125 values were used to define complete remission. Partial remission was defined as an incomplete response to therapy documented by the treating physician. Other variables included age and stage at diagnosis, race/ethnicity, Charlson’s comorbidity index, neighborhood deprivation index and prior membership. Modified Poisson regression with robust error variance was used to evaluate the association for the pandemic period and race/ethnicity with the remission outcomes. Results: Of 728 patients included, 531 and 197 patients were diagnosed in the pre-pandemic and pandemic periods, respectively. The distributions of the patients’ age, race, and stage were similar between the pre-pandemic and pandemic period. The cohort was racially/ethnically diverse: 46.0% White, 33.5% Hispanic, 7.4% Black, and 13.1% Asian. Complete remission was observed in 406 (76.5%) patients in the pre-pandemic period compared to 149 (75.6%) patients in the pandemic period (p=0.82). Clinical remission was observed in 473 (89.1%) patients in per-pandemic and 176 (89.34%) patients in pandemic period (p=0.92). No statistically significant associations were found between the remission outcomes and the pandemic in the adjusted models. Black patients had lower complete remission rates (but not lower clinical remission rates) compared to White patients in the pandemic period (p=0.06). Of note, Black patients had 67.6% complete remission rate in the pre-pandemic period whereas only 35.3% achieved complete remission in the pandemic period (p=0.01). However, the number of Black patients in the pandemic period was small (N=17). Conclusions: Overall, patients diagnosed with ovarian cancer achieved similar complete and clinical remission rates between the pre-pandemic and pandemic period. Complete remission varies across subgroups of patients. This finding needs to be further investigated with a larger sample.
Association of socioeconomic status (SES) with use of specialist palliative care (SPC) among people who died with cancer before and during the COVID-19 pandemic.
Authors: Javaid Iqbal, Rahim Moineddin, Robert Fowler, Monika K. Krzyzanowska, Christopher M. Booth, James Downar, Jenny Lau, Lisa W Le, Gary Rodin, Hsien Seow, Peter Tanuseputro, Craig Earle, Kieran Quinn, Breffni Hannon, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2023)

e18504 Background: Access to high-quality care, including SPC, is known to vary according to SES. The effect of SES on access to SPC during the COVID-19 pandemic remains unknown. We measured the association of SES with SPC use in different care settings among people who died with cancer before and during the COVID-19 pandemic. Methods: This retrospective, population-based cohort study included 173,915 adult patients who died with cancer from 16/3/2015 to 15/3/2020 (pre-pandemic), and from 16/3/2020 to 15/3/2021 (pandemic period), in Ontario, Canada; March 16, 2020 coincided with the start of pandemic-related hospital entrance screening. The primary outcome was access to SPC in the last 30 days of life, measured as the percentage of people with at least one SPC visit and the rate of visits/patient/30 days across home, hospital inpatient, and outpatient care settings. We used an interrupted time series analysis with segmented linear regression accounting for serial correlation to examine the immediate and gradual changes due to the pandemic. Analyses were stratified by SES, defined using area-level material deprivation quintiles (Q1, least to Q5, most deprived). Results: In total, 100,462 (57.8%) people received SPC in the last 30 days of life. The access to SPC increased steadily by 0.13% per 30 days over the pre-pandemic period ( P&lt;0.001), with a drop of 5.34% at the start of pandemic ( P&lt;0.001) and a trend increase of 0.19% during the pandemic period ( P = 0.10). The table shows study outcomes by care setting and SES. At baseline, patients in Q5 (vs Q1) had lower rates of SPC home visits, while rates of inpatient visits and outpatient visits were similar. Pre-pandemic for Q1 and Q5, inpatient visits were decreasing, outpatient visits were increasing, and home visits were stable. For both Q1 and Q5, there was an immediate decrease in home visits and increase in outpatient visits at pandemic onset, followed by a recovery in home visits; trends for inpatient and outpatient visits were unchanged. Conclusions: The COVID-19 pandemic led to an immediate decrease in access to SPC among people who died with cancer, particularly for home visits. SES was significantly associated with access to home visits, both before and during the pandemic. [Table: see text]
CCTG HN11: SPECT-CT guided elective contralateral neck treatment (SELECT) for patients with lateralized oropharyngeal cancer—A phase III randomized controlled trial.
Authors: John R. de Almeida, Wendy R. Parulekar, Apostolos Christopoulos, Isabelle C Gauthier, Rosemary Martino, Andrea McNiven, Anthony C. Nichols, Ambika Parmar, Eitan Prisman, Jolie Ringash, Martin Smoragiewicz, Rathan M. Subramaniam, John Waldron, Steven B. Chinn, James Edward Bates, Kate Whelan, Wei Tu, Ali Hosni
Journal: Journal of Clinical Oncology (2023)

TPS6114 Background: Lymphatic mapping identifies neck lymph nodes at risk for cancer spread in patients with lateralized oropharyngeal (OPC) squamous cell carcinoma. We hypothesize that a lymphatic mapping guided approach to radiotherapy (RT) treatment of the contralateral neck will enable safe de-escalation of therapy with acceptable disease control with potential benefits in RT related toxicity, QOL, swallowing function and economics. Methods: HN.11 is a Canadian Cancer Trials Group international multi-centre, non-inferiority randomized phase III trial comparing a lymphatic mapping-guided approach for management of the contralateral neck (experimental) vs. bilateral neck radiation therapy (RT) (control). The primary objective is to determine if a lymphatic mapping-guided approach for management of the contralateral neck has a non-inferior disease-free survival (DFS) compared to bilateral neck RT. Secondary objectives: To compare swallowing related QOL, xerostomia, isolated contralateral neck failure, overall survival, loco-regional failure, distant metastases, RT-related toxicities, patient reported adverse events (PRO CTCAE), gastrostomy tube usage, and economics indicators (resource utilization, lost productivity, financial toxicity, EQ5D). Exploratory objectives: Swallowing function using video fluoroscopic swallow studies, head and neck-cancer specific QOL, patterns of lymphatic drainage, radiomic prediction of contralateral lymphatic drainage, correlation of tumour somatic mutations and ctDNA with disease recurrence. Statistical Design: The target sample size is 510 patients. The experimental arm will be considered non-inferior if the upper limit of the one sided 95% confidence interval (CI) of the estimated hazard ratio (HR) does not exceed 1.46 (non-inferiority margin of 6.5% for 2-year DFS). In the primary intention-to-treat (ITT) analysis, the study has 81% power, with a one-sided type I error rate of 5%, assuming 5 years of accrual, 3-years of follow up to observe 178 DFS events, and a 5% loss to follow up. If non-inferiority is demonstrated in the ITT analysis, a secondary per-protocol analysis will be performed, analyzing those patients treated as per their allocation, with 80% power to detect non-inferiority of the experimental arm assuming a conservative 10% cross-over from the experimental to the control arm (i.e. failed lymphatic mapping). Conduct to Date: Study activation September 29, 2022. First enrollment was February 10, 2023. Supported by Canadian Cancer Society, Canadian Institutes of Health Research, National Cancer Trials Network (NCTN). Clinical trial information: NCT05451004 .
Neoadjuvant pembrolizumab, GX-188E, and GX-I7 in patients with human papillomavirus-16- and/or 18-positive head and neck squamous cell carcinoma: Single-arm, phase 2 trial with single cell transcriptomic analysis and artificial intelligence-powered spatial analysis.
Authors: Hye Ryun Kim, Chang Gon Kim, June-Young Koh, Min Hee Hong, Hyun Jun Hong, DaHee Kim, Nam Suk Sim, Sun Och Yoon, Gamin Kim, Jung Eun Lee, Wonrak Son, Chang Lee, Kyung Hwan Kim, Jeong Seok Lee, Donggeun Yoo, Chan-Young Ock, Yoon Woo Koh
Journal: Journal of Clinical Oncology (2023)

6075 Background: With the increasing prevalence of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection, effective treatment strategies for HPV-positive HNSCC are urgently needed. Here, we present the results of neoadjuvant checkpoint blockade of pembrolizumab, therapeutic HPV DNA vaccine of GX-188E, and long-acting interleukin-7 of GX-I7 for patients with resectable HPV-16 and/or 18-positive HNSCC. Methods: In this single-arm, phase 2 trial, patients with resectable HPV-16 and/or 18-positive HNSCC were enrolled. Patients were given pembrolizumab 200mg on day 1 and day 22; GX-188E 2mg on day 1, 8, and 22; and GX-I7 1200 ug/kg on day 8 before surgical resection. Major pathologic response (MPR; defined as residual viable tumor of less than or equal to 10%) was primary endpoint with null and alternative hypothesis of MPR rate ≤5% and ≥35%, respectively. Secondary objectives were safety, recurrence, and survival. Results: Of the 11 patients included, all underwent surgical resection after neoadjuvant treatment without delays in surgery or increased surgical complications. MPR was achieved in seven patients (63.6%) and pathologic complete response was achieved in four patients (36.3%), which met the primary endpoint. Single cell RNA sequencing of baseline and post-treatment paired specimens revealed that the proportion of follicular helper T cell cluster, featured with CXCR5 and BCL6 expression, was significantly increased among tumor-infiltrating immune cells, accompanied with the reinvigoration of CD8 T cell cluster toward less exhausted phenotypes, represented with the upregulation of TCF7 and CD28 expression. In addition, artificial intelligence-powered spatial analysis revealed that triple combination significantly increased the density of tumor-infiltrating lymphocytes, completely converting immune-desert and immune-excluded type of tumor to inflamed immune phenotype. Conclusions: Neoadjuvant pembrolizumab, GX-188E, and GX-I7 showed promising activity and manageable safety profile in patients with resectable HPV-16 and/or 18-positive HNSCC. Therapeutic induction of brisk immune responses significantly reshaped the tumor microenvironment and associated with pathologic regression, warranting further investigation of pembrolizumab, GX-188E, and GX-I7 for patients with HPV-positive HNSCC. Clinical trial information: NCT05286060 .